You Don't Muck with MYC

Abstract

MYC homeostasis is critical for major cellular and organismal processes. The physiological and pathologic patterns of c-myc transcription are programmed by a large number of cis-elements and transfactors (RNAs and proteins). These elements and factors receive inputs from a multitude of intracellular and extracellular pathways. Because c-myc regulation has customarily been dissected element by element and factor by factor, it has been difficult to appreciate how the c-myc promoter and regulatory sequences operate as a system. A full accounting of the regulation of c-myc transcription will require an understanding of the dynamic interplay of these factors and elements with one another, with chromatin, and with the changes in DNA structure and topology that are inevitably coupled with gene activity.

Figure 1.

Partial list of factors and relative binding sites (not to scale).^,

Figure 2.

Requiring multiple activator-dependent steps to ratchet the RNA polymerase through multiple steps and then to promoter escape decreases intrinsic noise compared to a single rate-determining step. A single strong activator could act repetitively.

Figure 3.

Multiple factors acting through suboptimal sites averages multiple inputs and decreases extrinsic noise.